Treatment-resistant depression: what it means and when to ask about Spravato

If you have tried more than one antidepressant and still do not feel like yourself, you are not alone, and it is not a personal failure. Depression is common, and many people need more than one approach before they find relief. When symptoms keep coming back despite real effort, it may be time for a closer look at what is going on and what other options exist, including SPRAVATO® (esketamine) nasal spray.

What “treatment-resistant” actually means

Treatment-resistant depression (TRD) is a clinical term, not a label about you. It is most often used when major depression has not improved enough after at least two different antidepressants, each taken at an adequate dose for an adequate length of time during the current episode. Large studies have found that only about a third of people reach full remission with their first antidepressant, so needing a second or third step is a very ordinary part of depression care.

“Resistant” also does not mean “hopeless.” It means the first approaches did not do enough, and it is worth widening the lens. Learn more about our approach to depression and anxiety treatment.

What a careful review looks at first

Before deciding that depression is treatment-resistant, a thorough psychiatric provider will usually revisit the basics. A good review often includes:

• The diagnosis itself: whether bipolar disorder, PTSD, ADHD, or another condition could be part of the picture.
• Each past medication trial: the dose, how long it was taken, side effects, and why it was stopped.
• Medical factors: thyroid problems, anemia, sleep apnea, chronic pain, and other medications that can affect mood.
• Alcohol, cannabis, and other substances, which can blunt treatment response.
• Sleep, stress, and support: life circumstances that keep depression going.
• Therapy: whether evidence-based therapy has been part of the plan alongside medication.

Sometimes this review points to a simpler fix, such as a dose adjustment or treating an overlooked condition. Changes like these should always be made with your prescriber, never on your own. If you want a snapshot of where your mood is today, our free PHQ-9 depression screening takes about two minutes.

Where Spravato fits

SPRAVATO® (esketamine) is an FDA-approved nasal spray for adults with treatment-resistant depression. It is also approved, together with an oral antidepressant, for adults with major depressive disorder who have acute suicidal thoughts or behavior. It works differently from traditional antidepressants, acting on the brain’s glutamate system, which is one reason it may be considered when other medications have not helped enough.

Because of how it works, Spravato is given in a specific, carefully supervised way:

• It is self-administered under direct supervision in a certified healthcare setting, under a safety program called the SPRAVATO REMS. It is never taken home.
• Patients are monitored for at least 2 hours after each dose.
• Patients should not drive or operate machinery until the next day, after a restful night of sleep, so a ride home is needed.
• Possible risks include sedation, dissociation (feeling disconnected or “out of body”), increased blood pressure, and potential for misuse. Blood pressure is checked before and after each dose.

Spravato is not right for everyone. Some heart, blood vessel, and other medical conditions can make it unsafe, and a history of certain substance use needs careful discussion. Curious what an actual session involves? Read what a Spravato treatment day looks like.

Signs it may be time to ask

It may be worth asking a psychiatric provider about Spravato and other next-step options if:

• You have tried two or more antidepressants without enough improvement.
• Side effects have made it hard to stay on medications long enough to help.
• You feel somewhat better but still not like yourself, months into treatment.
• Depression keeps returning, even when you are doing everything recommended.

Other next steps may also be discussed, such as adjusting or combining medications, adding focused therapy, or GeneSight pharmacogenomic testing in some cases. The right path depends on your history and goals.

If you are having thoughts of suicide or self-harm, call or text 988 (the Suicide and Crisis Lifeline) or call 911 right away. Spravato is not an emergency treatment and does not replace crisis care.

Find out whether Spravato is right for you

Dr. Iman Yunis, DNP, PMHNP-BC, is a board-certified psychiatric mental health nurse practitioner with a focus on treatment-resistant depression and Spravato care for adults across Washington, including Seattle and South King County. A telehealth evaluation with Dr. Yunis reviews your full history, past treatments, and medical factors to help you understand whether Spravato may be a fit and what your other options are. Learn more on our Spravato treatment page.

SPRAVATO® is a registered trademark of Johnson and Johnson.